tbuckley/cabot-search huggingface dataset:
POS0214 CORONARY MICROVASCULAR DYSFUNCTION IN PATIENTS WITH RHEUMATOID ARTHRITIS AND DIABETES MELLITUS: A CROSS-SECTIONAL STUDY WITH 13NH3 MYOCARDIAL PET/CT
Authors: B. Dijkshoorn, R. Knol, F. van der Zant, M. Nurmohamed, S. Simsek
Journal: Annals of the Rheumatic Diseases (2022)

Background Patients with rheumatoid arthritis (RA) are at increased risk of cardiovascular disease. This risk is similar to that of diabetes mellitus (DM). There have been no studies comparing the coronary microvascular dysfunction assessed with coronary flow reserve (CFR) of RA patients to both patients with DM and a control group (=patients without RA, without DM and no cardiovascular event). Objectives To assess the difference in coronary microvascular dysfunction in patients with RA in comparison to patients with DM and control group. Methods From our 13NH3 myocardial PET/CT registry we included all patients that were included from December 2013 until March 2019. A total of 33 patients with RA, 299 patients with DM and 179 control patients (=patients without RA and without DM) were analyzed. Myocardial blood flow was quantified at rest and under stress induced by administrating adenosine. Coronary flow reserve was calculated by dividing MBF under stress by MBF in rest. CFR &lt; 2 was indicative for coronary microvascular dysfunction. Results The mean age of patients was 66, with more females in the RA and control group vs the DM group (67% and 69% vs 49% respectively). The total MBF, under adenosine administration, measured in RA patients was higher than DM patients albeit that this did not reach statistical significance (2.26 ± -,70 vs 2,05 ± 0,63 mL/min/g, p=0.08). When compared to controls, the MBF of RA patients was significantly lower (2,94 ± 0,44 vs 2,26 ± 0,70, p &lt; 0.001). The coronary flow reserve (CFR) of patients with RA was similar to patients with DM (2.20 ± 0,69 vs 2,21 ± 0,70 mL/min/g, p=0.977). The CFR of the control group was significantly higher than those of the RA patients (3,03 ± 0,64 vs 2.20 ± 0,69 mL/min/g, p&lt;0.000) and of the DM patients (3,03 ± 0,64 vs 2.21 ± 0,70 mL/min/g, p&lt;0.000). 42% of RA- and 38% of DM patients had coronary microvascular dysfunction, compared to 4% in the control group. Conclusion Our results indicate an impaired coronary blood flow in both patients with RA and DM in similar levels. Both patient groups had significantly more coronary microvascular dysfunction. Disclosure of Interests Bas Dijkshoorn: None declared, Remco Knol: None declared, Friso van der Zant: None declared, Michael Nurmohamed Speakers bureau: Abbvie, Janssen, Celgene, Consultant of: Abbvie, Grant/research support from: Abbvie, Amgen, Pfizer, Galapagos, BMS, Suat Simsek: None declared
POS0030 CLINICAL AND GENETIC FACTORS ASSOCIATED WITH RADIOGRAPHIC PROGRESSION IN PATIENTS WITH ANKYLOSING SPONDYLITIS
Authors: B. Nam, S. Y. Bang, Y. Park, S. Jo, J. H. Shin, S. Lee, K. B. Joo, T. H. Kim
Journal: Annals of the Rheumatic Diseases (2022)

Background Ankylosing spondylitis (AS) is a heritable inflammatory disease eventually leading to spinal fusion 1 . Severity of structural damage is highly variable, some patients develop almost no change in spinal structure for long disease duration, whereas others have total ankylosis even in the early stage of disease. Objectives To identify clinical and genetic factors associated with severe radiographic damage in patients with AS. Methods We newly generated genome-wide variant data (833K, KoreanChip) of 444 AS patients. The severity of radiographic damage was assessed using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). To identify clinical and genetic factors associated with severe radiographic damage, multiple linear regression analyses were performed. Human AS osteoprogenitor cells were used for functional validation. Pathway analysis was also conducted. Results A total 444 AS patients (male 90.3%) were enrolled. The median mSASSS at baseline was 7.7 (5.5-16.8). The patients were observed for 9.6 (7.9-11.3) years. Within this period, the median mSASSS score increased to 14.0 (7.0-36.8). The most influential clinical factor of final mSASSS was baseline mSASSS (β = 0.818, p &lt; 0.001). Peripheral joint involvement was associated with decreased possibility of severe radiographic damage (β = -0.221, p &lt; 0.001). Eye involvement, longer follow up duration, and increased age at enrollment were associated with increased final mSASSS (β = 0.165, p &lt; 0.001; β = 0.039, p &lt; 0.001; β = 0.010, p = 0.002, respectively). Ryanodine receptor 3 (RYR3) gene was associated with severe radiographic damage (β = 1.105, p = 1.97x10-06). Treatment with Rhodamine B, a ligand of RYR3, induced extracellular matrix mineralization of AS osteoprogenitors in vitro. For the pathway analysis, PI3K-Akt signaling pathway and focal adhesion pathway were associated with severe radiographic damage in AS. Conclusion This study identified clinical and genetic factors that contributed to better understanding of the pathogenesis and biology associated with radiographic damage in AS. References [1]Li Z, Brown MA. Progress of genome-wide association studies of ankylosing spondylitis. Clinical &amp; Translational Immunology. 2017;6(12):e163. Disclosure of Interests None declared
OP0307 PULMONARY FIBROSIS IN EARLY RHEUMATOID ARTHRITIS IN RELATION TO GENETIC LOCI AND INDIVIDUAL ACPA SPECIFICITIES
Authors: M. Brink, L. Ljung, M. Hansson, J. Rönnelid, R. Holmdahl, K. Skriner, G. Serre, L. Klareskog, S. Rantapää Dahlqvist
Journal: Annals of the Rheumatic Diseases (2022)

Background Pulmonary manifestations in rheumatoid arthritis (RA) are common comorbidities but the underlying mechanisms are largely unknown. We found in a previous study 3 SNPs associated with pulmonary fibrosis (PF); rs35705950 (MUC5B), rs111521887 (TOLLIP), and rs2609255 ( FAM13A ) besides age, rheumatoid factor positivity and methotrexate treatment. Objectives To evaluate for the added value of a multiplex of anti-citrullinated peptide antibodies (ACPA) for the development of pulmonary fibrosis (PF) in an inception cohort of RA patients. Methods A total of 1184 patients with early RA were consecutively included and followed prospectively from the date of diagnosis (index date) until death or until 31 December 2016. The diagnosis of PF was based on high resolution tomography. The presence of 21 ACPA fine specificities were analysed in plasma sampled at index date, using a custom-made microarray chip (Thermo Fisher Scientific, Uppsala, Sweden). Data on both ACPA and genetic data was available for 841 RA patients, of whom 50 developed PF. Associations were analysed using logistic regression analysis and presented as the odds ratio (OR) with the 95% confidence interval (CI). Models were adjusted for sex, age, DAS28 and presence of RF at RA diagnosis, smoking ever, and HLA-SE and in a second step for the three SNPs (.rs35705950, rs111521887 and rs2609255), respectively. Results In unadjusted analyses eight ACPA reactivities were found associated with PF development (p&lt; 0.05-0.001). The number of ACPA reactivities was related to PF development, both in crude and adjusted models (p&lt;0.05 for both). In models concomitantly adjusted for the three SNPs (rs35705950, rs111521887 and rs2609255) respectively, in addition to mentioned adjustments the number of ACPA reactivities (p&lt;0.05 for all three nmodels), Vim60-75 (p&lt;0.05, in all three models), Fibβ62–78 (72) (p&lt;0.001-p&lt;0.05) and F4-CIT-R (p&lt;0.01-p&lt;0.05) were all found significantly associated to PF development irrespective of the SNPs. Conclusion The development of PF in an inception cohort of RA patients was associated both with risk genes and, independently of the risk genes, the presence of certain ACPA, and the number of ACPA reactivities. References [1]Jönsson E, et al. Pulmonary fibrosis in relation to genetic loci in an inception cohort of patients with early rheumatoid arthritis from northern Sweden. Rheumatology (Oxford). 2021 May 16:keab441. doi: 10.1093/rheumatology/keab441. Acknowledgements I have no acknowledgements to declare. The staff and patients at the departments of rheumatology in northern Sweden. Disclosure of Interests None declared
POS0218 DECREASED miR-122-5p IN NEUTROPHIL-DERIVED EXOSOMES ATTENUATED IMMUNOREGULATORY FUNCTION ON MACROPHAGES BY TARGETING IRF5 EXPRESSION IN BEHCET’S DISEASE
Authors: X. Yu, C. Li, J. Liu, H. Chen, W. Zheng
Journal: Annals of the Rheumatic Diseases (2022)

Background Behçet’s disease (BD) is a chronic systemic vasculitis characterized by the overactivation of neutrophils and macrophages. Exosomes are membrane-derived vesicles that mediate intercellular communications and neutrophil-derived exosomes account for the major portion of serum exosomes in BD. However, the role of neutrophil-derived exosomes in BD remains unknown. Objectives 1) To investigate the production of exosomes by BD neutrophils; 2) To elucidate the regulation of macrophage by BD neutrophil-derived exosomes; 3) To explore the mechanism of immunoregulatory functions of BD neutrophil-derived exosomes. Methods BD and healthy control (HC) neutrophil-derived exosomes were extracted and quantified. Human monocyte-derived macrophages (HMDM) were stimulated with BD and HC neutrophil-derived exosomes, and TNF-α and IL-6 production were examined. Differently expressed miRNAs in BD neutrophil-derived exosomes were analyzed using miRNA sequencing. LPS-induced HMDM were treated with miRNA mimics or inhibitors, and TNF-α and IL-6 production were detected. miRNA was overexpressed in macrophages, and RNA sequencing was performed to analyze regulating pathways. Dual-luciferase assays were performed to confirm miRNA-mRNA interaction. Results BD neutrophils produced a significantly lower level of exosomes than HC ones. Both BD and HC neutrophil-derived exosomes suppressed TNF-α and IL-6 production by macrophages, but to a lesser extent by BD neutrophil-derived exosomes. Six downregulated miRNAs were presented in BD neutrophil-derived exosomes, including miR-122-5p. miR-122-5p mimics inhibited IL-6 and TNF-α production while miR-122-5p inhibitor promoted IL-6 and TNF-α production by HMDMs. Overexpression of miR-122-5p attenuated TLR4 and IFN-β signaling. miR-122-5p directly targeted 3’UTR of IRF5, the TF regulating TLR4 pathway and autocrine of IFN-β, and downregulated IRF5 expression confirmed by dual luciferase assay. Knocking down IRF5 dampened IL-6 and TNF-α production in HMDMs. Figure 1. (A) Decreased production of BD neutrophil-derived exosomes. (B) Reduced suppression of macrophage activation by BD neutrophil-derived exosomes. (C) Differentially expressed miRNAs (downregulated) in BD neutrophil-derived exosomes. (D) miR-122-5p suppressed TLR4 and JAK-STAT signaling in HMDM. (E) miR-122-5p inhibited activation of HMDM. (F) miR-122-5p inhibited IRF5 expression in HMDM. Conclusion Our findings suggested the reduced production and immunoregulatory function of BD neutrophil-derived exosomes, mediated by lower levels of miR-122-5p in neutrophil-derived exosomes. Impaired BD neutrophil-derived exosomes might be implicated in the overactivation of macrophages in BD. References [1]Kolonics, Ferenc et al. Cells vol. 9,12 2718. 18 Dec. 2020, Disclosure of Interests None declared
POS0149 WHAT IS BACKFILL? - DETAILED CT / MRI ANALYSIS OF NEW BONE FORMATION IN AXIAL SPONDYLOARTHRITIS
Authors: T. Diekhoff, C. Niedermeier, F. Proft, D. Poddubnyy, K. G. Hermann
Journal: Annals of the Rheumatic Diseases (2022)

Background Several magnetic resonance imaging (MRI) findings of the sacroiliac joint space in axial spondyloarthritis (axSpA) were previously described such as inflammation or fatty metaplasia inside an erosion, i.e. “backfill”. However, it is incompletely understood if one or all of these changes represent calcified bone matrix. Objectives This study aims to one-by-one link the aforementioned changes to computed tomography (CT) measurements and to understand, which of those findings represents new bone formation. Methods Out of 178 patients from two prospective studies that included CT and MRI of the sacroiliac joints all patients with the final diagnosis of axSpA were selected. MRI was screened by two senior musculoskeletal radiologists in consensus for joint-space related MRI findings and grouped into three categories, Type A: hyperintense in STIR and hypointense in T1 (inflammation inside erosion), Type B: hyperintense in both sequences and Type C: hypointense in STIR and hyperintense in T1 (backfill). By using image fusion techniques and one-by-one comparison, the Hounsfiled Units (HU) of those lesions as well as normal cartilage and spongeous and cortical bone were measured in CT. Results Ninety-nine patients with axSpA were identified and 48 Type A, 88 Type B and 84 Type C lesions were assessed. Please see Figure 1 for CT measurements. The HU values of cartilage were 73.6±15.0, spongious bone 188.0±69.9, cortical bone 1086.0±100.3, Type A 341.2±96.7, Type B 359.3±153.5 and Type C 446.8±123.0, respectively. The lesion values were significantly higher than cartilage and spongious bone but lower than cortical bone (p&lt;0.001). Type A and B showed similar HU (p=0.93), whereas Type C lesions where denser (p&lt;0.001). Figure 1. CT-Measurements of cartilage, bone and lesions. Conclusion All joint space lesions (Type A to C) show calcified matrix and, thus, resemble new bone formation with gradually more calcified matrix in Type C lesions, i.e. typical backfill. Therefore, the nomenclature of those lesions should be critically re-assessed. Disclosure of Interests None declared
Incidence and characteristics of pseudoprogression in IDH-mutant high-grade gliomas: A POLA network study
Authors: Antoine Seyve, Caroline Dehais, Olivier Chinot, Apolline Djelad, Elisabeth Cohen-Moyal, Charlotte Bronnimann, Carole Gourmelon, Evelyne Emery, Philippe Colin, Mathieu Boone, Elodie Vauléon, Olivier Langlois, Anna-Luisa di Stefano, Romuald Seizeur, François Ghiringhelli, Anne D’Hombres, Loic Feuvret, Jacques Guyotat, Laurent Capelle, Catherine Carpentier, Louis Garnier, Jérôme Honnorat, David Meyronet, Karima Mokhtari, Dominique Figarella-Branger, François Ducray
Journal: Neuro-Oncology (2022)

Incidence and characteristics of pseudoprogression in isocitrate dehydrogenase-mutant high-grade gliomas (IDHmt HGG) remain to be specifically described.We analyzed pseudoprogression characteristics and explored the possibility of pseudoprogression misdiagnosis in IDHmt HGG patients, treated with radiotherapy (RT) (with or without chemotherapy [CT]), included in the French POLA network. Pseudoprogression was analyzed in patients with MRI available for review (reference cohort, n = 200). Pseudoprogression misdiagnosis was estimated in this cohort and in an independent cohort (control cohort, n = 543) based on progression-free survival before and after first progression.In the reference cohort, 38 patients (19%) presented a pseudoprogression after a median time of 10.5 months after RT. Pseudoprogression characteristics were similar across IDHmt HGG subtypes. In most patients, it consisted of the appearance of one or several infracentimetric, asymptomatic, contrast-enhanced lesions occurring within 2 years after RT. The only factor associated with pseudoprogression occurrence was adjuvant PCV CT. Among patients considered as having a first true progression, 7 out of 41 (17%) in the reference cohort and 35 out of 203 (17%) in the control cohort were retrospectively suspected to have a misdiagnosed pseudoprogression. Patients with a misdiagnosed pseudoprogression were characterized by a time to event and an outcome similar to that of patients with a pseudoprogression but presented with larger and more symptomatic lesions.In patients with an IDHmt HGG, pseudoprogression occurs later than in IDH-wildtype glioblastomas and seems not only frequent but also frequently misdiagnosed. Within the first 2 years after RT, the possibility of a pseudoprogression should be carefully considered.
Distinct transcriptomic and metabolomic profiles characterize NSAID-induced urticaria/angioedema patients undergoing aspirin desensitization
Authors: Sen Hee Tay, Amelia Santosa, Eugene Chen Howe Goh, Chun Xiang Xu, Lik Hang Wu, Mei Bigliardi-Qi, Leroy Sivappiragasam S/O. Pakkiri, Bernett Teck Kwong Lee, Chester Lee Drum, Paul Lorenz Bigliardi
Journal: Journal of Allergy and Clinical Immunology (2022)

There is limited data on the mechanisms of aspirin desensitization in patients with nonsteroidal anti-inflammatory drug (NSAID)-induced urticaria/angioedema (NIUA).We sought to characterize the transcriptomic and metabolomic profiles of patients with NIUA undergoing aspirin desensitization.PBMCs and plasma were separated from the blood of patients with NIUA undergoing aspirin desensitization for coronary artery disease and NSAID-tolerant controls. RNA was isolated from PBMCs and subjected to messenger RNA (mRNA)- and long noncoding RNA (lncRNA)-sequencing. Plasma samples were analyzed using LC-MS/MS for metabolite shifts using a semitargeted metabolomics panel.Eleven patients with NIUA and 10 healthy controls were recruited. The mRNA gene profiles of predesensitization versus postdesensitization and healthy control versus postdesensitization did not differ significantly. However, we identified 739 mRNAs and 888 lncRNAs as differentially expressed from preaspirin desensitization patients and controls. A 12-mRNA gene signature was trained using a machine learning algorithm to distinguish between controls, postdose, and predose samples. Ingenuity Pathway Analysis identified 5 canonical pathways that were significantly enriched in preaspirin desensitization samples. IL-22 was the most upregulated pathway. To investigate the potential regulatory roles of the differentially expressed lncRNA on the mRNAs, 9 lncRNAs and 12 mRNAs showed significantly correlated expression patterns in the IL-22 pathway. To validate the transcriptomics data, IL-22 was measured in the plasma samples of the subjects using ELISA. IL-22 was significantly higher in preaspirin desensitization patients compared with controls. In parallel, metabolomic analysis revealed stark differences in plasma profiles of preaspirin desensitization patients and healthy controls. In particular, 2-hydroxybenzoic acid (salicylic acid) was significantly lower in preaspirin desensitization patients compared with healthy controls.This is the first study to combine both transcriptomic and metabolomic approaches in patients with NIUA, which contributes to a deeper understanding about the pathogenesis of NIUA and may potentially pave the way toward a molecular diagnosis of NSAID hypersensitivity.
Mycoplasma pneumoniae beyond the COVID-19 pandemic: where is it?
Authors: Patrick M Meyer Sauteur, Victoria J Chalker, Christoph Berger, Ran Nir-Paz, Michael L Beeton, Sabine Pereyre, Cécile Bébéar, Noémie Wagner, Corinne Andreutti, Gilbert Greub, Philipp K A Agyeman, Christoph Aebi, Michael Buettcher, Lisa Kottanattu, Valeria Gaia, Frank Imkamp, Reinhard Zbinden, Semjon Sidorov, Anita Niederer-Loher, Florence Barbey, Adrian Egli, Ulrich Heininger, Chloé Schlaeppi, Cihan Papan, Malte Kohns Vasconcelos, Birgit Henrich, Colin Mackenzie, Roger Dumke, Gerlinde Schneider, Nathalie Bossuyt, Melissa Vermeulen, Katherine Loens, Mireille van Westreenen, Nelianne J Verkaik, Annemarie M C van Rossum, Jessica Day, Baharak Afshar, Ville Peltola, Santtu Heinonen, Marjo Renko, Terhi Tapiainen, Henrik Døllner, Fernanda Rodrigues, Minos Matsas, Eleni Kalogera, Evangelia Petridou, Ioannis Kopsidas, Theoklis E Zaoutis, Darja Keše, Hila Elinav, Ayelet Michael-Gayego, Ho Namkoong, Yu-Chia Hsieh, Matthias Maiwald, Liat Hui Loo, Rama Chaudhry, Larry K Kociolek, Nadia Rodríguez, David Lorenz, Matthew Blakiston
Journal: The Lancet Microbe (2022)
Mepolizumab for urban children with exacerbation-prone eosinophilic asthma in the USA (MUPPITS-2): a randomised, double-blind, placebo-controlled, parallel-group trial
Authors: Daniel J Jackson, Leonard B Bacharier, Peter J Gergen, Lisa Gagalis, Agustin Calatroni, Stephanie Wellford, Michelle A Gill, Jeffrey Stokes, Andrew H Liu, Rebecca S Gruchalla, Robyn T Cohen, Melanie Makhija, Gurjit K Khurana Hershey, George T O'Connor, Jacqueline A Pongracic, Michael G Sherenian, Katherine Rivera-Spoljaric, Edward M Zoratti, Stephen J Teach, Meyer Kattan, Cullen M Dutmer, Haejin Kim, Carin Lamm, William J Sheehan, R Max Segnitz, Kimberly A Dill-McFarland, Cynthia M Visness, Patrice M Becker, James E Gern, Christine A Sorkness, William W Busse, Matthew C Altman
Journal: The Lancet (2022)
A decrease in functional microbiomes represented as <i>Faecalibacterium</i> affects immune homeostasis in long-term stable liver transplant patients
Authors: Soon Kyu Lee, JooYeon Jhun, Seung Yoon Lee, Sukjung Choi, Sun Shim Choi, Myeong Soo Park, Seon-Young Lee, Keun-Hyung Cho, A Ram Lee, Joseph Ahn, Ho Joong Choi, Young Kyoung You, Pil Soo Sung, Jeong Won Jang, Si Hyun Bae, Seung Kew Yoon, Mi-La Cho, Jong Young Choi
Journal: Gut Microbes (2022)

LT, liver transplantation; HCC, hepatocellular carcinoma; IS, immunosuppressants; DC, dendritic cells; Treg, regulatory T; Th17, T helper 17; AST, aspartate transaminase; ALT, alanine transaminase; OUT, operational taxonomic unit; LEfSe, linear discriminant analysis effect size; LDA, linear discriminant analysis; IL, interleukin; TGF, transforming growth factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN, interferon; TNF-α, tumor necrosis factor-α; MIP-1α, macrophage inflammatory protein-1α; IP-10, interferon γ-induced protein; MCP-1, monocyte chemoattractant protein-1; ACR, acute cellular rejection; NF-κB, nuclear factor κB; PT INR, prothrombin time; QC, quality check; PBMC, peripheral blood mononuclear cells; PBS, phosphate-buffered saline; ELISA, enzyme-linked immunosorbent assay.
Early drug development in solid tumours: analysis of National Cancer Institute-sponsored phase 1 trials
Authors: Dai Chihara, Ruitao Lin, Christopher R Flowers, Shanda R Finnigan, Lisa M Cordes, Yoko Fukuda, Erich P Huang, Larry V Rubinstein, Loretta J Nastoupil, S Percy Ivy, James H Doroshow, Naoko Takebe
Journal: The Lancet (2022)
NF-κB: blending metabolism, immunity, and inflammation
Authors: Daria Capece, Daniela Verzella, Irene Flati, Paola Arboretto, Jessica Cornice, Guido Franzoso
Journal: Trends in Immunology (2022)

The procurement and management of nutrients and ability to fight infections are fundamental requirements for survival. These defense responses are bioenergetically costly, requiring the immune system to balance protection against pathogens with the need to maintain metabolic homeostasis. NF-κB transcription factors are central regulators of immunity and inflammation. Over the last two decades, these factors have emerged as a pivotal node coordinating the immune and metabolic systems in physiology and the etiopathogenesis of major threats to human health, including cancer, autoimmunity, chronic inflammation, and others. In this review, we discuss recent advances in understanding how NF-κB-dependent metabolic programs control inflammation, metabolism, and immunity and how improved knowledge of them may lead to better diagnostics and therapeutics for widespread human diseases.
Forgiveness Is the Attribute of the Strong: Nonadherence and Regimen Shortening in Drug-sensitive Tuberculosis
Authors: Helen R. Stagg, Jennifer A. Thompson, Marc C. I. Lipman, Derek J. Sloan, Mary Flook, Katherine L. Fielding
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

"Forgiveness" charts the ability of a drug or regimen to withstand nonadherence without negative clinical consequences.